Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
other information
Study period:
No data
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Relevant methodological deficiencies: male mice only tested, administrated volume was higher than recommended, animals were sacrificed 6 hours after the last administration instead of 18-24 hours.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
only males were used, administrated volume was higher than recommended, animals were sacrificed 6 hours after the last administration instead of 18-24 hours.
Principles of method if other than guideline:
Method: described in Boller and Schmid (1970) and Schmid (1975)
GLP compliance:
no
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): cis-pentene-2 nitrile commercial
- Physical state: pale yellow liquid

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Carworth Farm Lane-Petter
- Age at study initiation: no data
- Weight at study initiation: 25-30 g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study: no
- Housing: no data
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
No data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used: arachis oil
- Justification for choice of solvent/vehicle: no data
- Concentration of test material in vehicle: 0.8 and 4 µL/mL
- Amount of vehicle (if gavage or dermal): 2 x 25 mL/kg
Details on exposure:
No details
Duration of treatment / exposure:
30 hours
Frequency of treatment:
2 administration (at 0 and 24 hour)
Post exposure period:
6 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
2 x 0.02 mL/kg and 2 x 0.1 mL/kg
Basis:
nominal conc.
No. of animals per sex per dose:
10 males per dose
Control animals:
yes, concurrent vehicle
Positive control(s):
Benzene (Prolabo, lot n° 79.018)
- Justification for choice of positive control(s): benzene is a recognised clastogenic substance
- Route of administration: oral (gavage)
- Doses / concentrations: 2 x 1.25 mL/kg

Examinations

Tissues and cell types examined:
bone marrow (2000 polychromatic erythrocytes per animal)
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
Based on a preliminary study.

DETAILS OF SLIDE PREPARATION:
Bone marrow was collected in calf embryo serum. After centrigation, the pellet was homogenized, applied to a slide and coloured with May Grünwald-Giemsa.

METHOD OF ANALYSIS:
1000 polychromatic erythrocytes were counted by 2 persons and a mean  value was calculated.
Evaluation criteria:
% of polychromatic erythrocytes with micronuclei
Statistics:
The % of polychromatic erythrocytes with micronuclei in the control and treated groups were compared with the Student t-test.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range:  2 x 0.25 and 2 x 0.1 mL/kg
- Clinical signs of toxicity in test animals: At 2 x 0.25 mL/kg, 4/5 animals died. At 2 x 0.1 mL/kg, no mortality was observed, but animals were 
prostrated during the hour following the administration.

RESULTS OF DEFINITIVE STUDY
- Induction of micronuclei (for Micronucleus assay): see Table 7.6.2/
- Ratio of PCE/NCE (for Micronucleus assay): no data
- Appropriateness of dose levels and route: no data
- Statistical evaluation: no statistically significant increase in the  number of micronuclei was observed in the treated animals.

Any other information on results incl. tables

Table 7.6.2/1: Results of in vivo micronucleus test with cis-pentene-2-nitrile

Group

Dose

No. of mice

% polychromatic erythrocytes with micronuclei

Control (arachis oil)

0

10

0.22 ± 0.08

Cis-pentene-2 nitrile com.

2 x 0.02 mL/kg

10

0.14 ± 0.04

Cis-pentene-2 nitrile com.

2 x 0.1 mL/kg

10

0.13 ± 0.07

Benzene

2 x 1.25 mL/kg

10

3.25 ± 0.72

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
In this study with Cis-pentene-2-nitrile commercial, there was not a significant increase in the frequency of micronucleated polychromatic
erythrocytes in bone marrow after treatment.
Executive summary:

In a Swiss CFLP mouse bone marrow micronucleus assay, 10 males/dose were treated by oral gavage with cis-pentene-2-nitrile commercial (purity unknown) at doses of 0, 2 x 0.02 and 2 x 0.1 mL/kg bw. Bone marrow cells were harvested at 6 hours post-treatment. The vehicle was arachis oil.

 

Cis-pentene-2-nitrile commercial was tested at an adequate dose (based on a preliminary study results). The positive control induced the appropriate response.There was not a significant increase in the frequency of micronucleated polychromatic erythrocytes in bone marrow after treatment.